The work described in this application is aimed at preparing optical sensors using imaging fibers for biomedical analysis. Imaging fibers are high density coherent optical arrays with thousands of individual micron-sized optical fibers drawn into a coherent bundle with a total diameter of 200-500 microns. Two approaches are taken and lead to sensors with very different uses. In the first approach, the imaging sensor is modified with a multitude of fluorescent indicating regions on the distal face. The fluorescent signal from each region is spatially resolved and can be detected with a CCD camera. In this way, multiple analytes can be monitored simultaneously using a single sensing substrate with extremely small dimensions. The planned work extends the capabilities of such sensors to genetic analysis. A novel approach is proposed in which sensors are prepared using bead libraries and in which the location of each sensing region is randomized. Using advanced pattern recognition schemes coupled with encoding, the sensors should be readily calibrated. The approach offers the potential to create high density sensor arrays capable of monitoring hundreds of analytes or gene sequences simultaneously. In addition, the extremely small overall size of the sensor enables sensitive measurements to be made on small (nanoliter) sample sizes. In the second approach, the array is coated with a thin polymer layer containing a single sensing material. The resulting sensor is a microarray containing thousands of 2-4 micron sensors. This microarray can be used to simultaneously view a biological specimen and measure chemical concentrations at the surface of the specimen. The work proposes to explore the ability of such microsensor arrays to view neuronal tissue and determine localized release of acetylcholine from individual cells in intact tissue. The ultimate goal of this work is to develop techniques for obtaining simultaneous morphological and chemical information using a minimally-invasive sensor. Such sensors could be used for in vivo biopsies, cell function and diagnosis as well as to address a wide variety of fundamental biomedical research problems.